title: Hematopoietic cell-restricted deletion of CD36 reduces high-fat diet-induced macrophage infiltration and improves insulin signaling in adipose tissue.
abstract: OBJECTIVE
  The fatty acid translocase and scavenger receptor CD36 is important in the recognition and uptake of lipids. Accordingly, we hypothesized that it plays a role in saturated fatty acid-induced macrophage lipid accumulation and proinflammatory activation.
  
  
  METHODS
  In vitro, the effect of CD36 inhibition and deletion in lipid-induced macrophage inflammation was assessed using the putative CD36 inhibitor, sulfosuccinimidyl oleate (SSO), and bone marrow-derived macrophages from mice with (CD36KO) or without (wild-type) global deletion of CD36. To investigate whether deletion of macrophage CD36 would improve insulin sensitivity in vivo, wild-type mice were transplanted with bone marrow from CD36KO or wild-type mice and then fed a standard or high-fat diet (HFD) for 20 weeks.
  
  
  RESULTS
  SSO treatment markedly reduced saturated fatty acid-induced lipid accumulation and inflammation in RAW264.7 macrophages. Mice harboring CD36-specific deletion in hematopoietic-derived cells (HSC CD36KO) fed an HFD displayed improved insulin signaling and reduced macrophage infiltration in adipose tissue compared with wild-type mice, but this did not translate into protection against HFD-induced whole-body insulin resistance. Contrary to our hypothesis and our results using SSO in RAW264.7 macrophages, neither saturated fatty acid-induced lipid accumulation nor inflammation was reduced when comparing CD36KO with wild-type bone marrow-derived macrophages.
  
  
  CONCLUSIONS
  Although CD36 does not appear important in saturated fatty acid-induced macrophage lipid accumulation, our study uncovers a novel role for CD36 in the migration of proinflammatory phagocytes to adipose tissue in obesity, with a concomitant improvement in insulin action.
authors.affiliation: Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Hayley T
authors.initials: HT
authors.lastname: Nicholls
authors.forename: Greg
authors.initials: G
authors.lastname: Kowalski
authors.forename: David J
authors.initials: DJ
authors.lastname: Kennedy
authors.forename: Steve
authors.initials: S
authors.lastname: Risis
authors.forename: Lee A
authors.initials: LA
authors.lastname: Zaffino
authors.forename: Nadine
authors.initials: N
authors.lastname: Watson
authors.forename: Peter
authors.initials: P
authors.lastname: Kanellakis
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Watt
authors.forename: Alex
authors.initials: A
authors.lastname: Bobik
authors.forename: Arend
authors.initials: A
authors.lastname: Bonen
authors.forename: Maria
authors.initials: M
authors.lastname: Febbraio
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Lancaster
authors.forename: Mark A
authors.initials: MA
authors.lastname: Febbraio
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D016026:Bone Marrow Transplantation; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D004041:Dietary Fats / Q000009:adverse effects*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019308:Palmitic Acid / Q000009:adverse effects; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013229:Stearic Acids / Q000009:adverse effects
chemical_list: D018955:CD36 Antigens; D004041:Dietary Fats; D007328:Insulin; D013229:Stearic Acids; D019308:Palmitic Acid